NM_012305.4:c.551C>G

Variant names:

• chr11-977172-C-G
• NM_012305.4:c.551C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012305.4(AP2A2):​c.551C>G​(p.Pro184Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,400 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

Genes affected

AP2A2 (HGNC:562): (adaptor related protein complex 2 subunit alpha 2) The protein encoded by this gene is a subunit of the AP-2 adaptor protein complex, which is involved in linking lipid and protein membrane components with the clathrin lattice. This interaction supports the formation of clathrin-coated vesicles, and the encoded subunit aids in the process by binding polyphosphoinositide-containing lipids in the cell membrane. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.551C>G	p.Pro184Arg	missense_variant	Exon 5 of 22	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.551C>G	p.Pro184Arg	missense_variant	Exon 5 of 22	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.551C>G	p.Pro184Arg	missense_variant	Exon 5 of 22	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.551C>G		non_coding_transcript_exon_variant	Exon 5 of 21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.551C>G		non_coding_transcript_exon_variant	Exon 5 of 21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.551C>G		non_coding_transcript_exon_variant	Exon 5 of 21			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.551C>G		non_coding_transcript_exon_variant	Exon 5 of 20			ENSP00000510648.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460400 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;T;T;.
Eigen	Benign	0.12
Eigen_PC	Benign	-0.039
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;.;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;.;.;M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.8	D;D;D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0020	D;D;D;D;D
Sift4G	Uncertain	0.027	D;D;D;D;D
Polyphen		0.95	P;.;.;P;.
Vest4		0.76
MutPred		0.59		Gain of MoRF binding (P = 0.0016);.;Gain of MoRF binding (P = 0.0016);Gain of MoRF binding (P = 0.0016);.;
MVP		0.58
MPC		0.81
ClinPred		0.99	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.52
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-977172;